methadone interaction

Prepared by: Tony Antoniou, Pharm.D., St. Michaels Hospital & Alice Tseng, Pharm.D., Toronto General Hospital, Toronto Page 1 of 12 December 2, 2004 www.tthhivclinic.com

ANTIRETROVIRAL-METHADONE INTERACTIONS

Antiretroviral Study Type Patient(s) Nature of interaction Recommendation

NNRTIs

Delavirdine1 Pharmacokinetic 16 HIV negative volunteers maintained on methadone and 15 controls, each treated with delavirdine 600 mg bid for 5 days.

Methadone did not alter pharmacokinetics of delavirdine or N-delavirdine. Effect of delavirdine on methadone not studied.

Since delavirdine an inhibitor of 3A4, monitor for symptoms of opiate toxicity (e.g. miosis, drowsiness, rate and depth of respiration, N/V, constipation, bradycardia, hypotension) until further data available.

Efavirenz2 Pharmacokinetic 11 patients on stable methadone maintenance, due to begin antiretroviral therapy with two reverse transcriptase inhibitors and efavirenz

EFV methadone Cmax (p=0.007) and methadone AUC by mean of 60%. 9/11 patients complained of symptoms of methadone withdrawal from day 8-10 onwards of starting efavirenz, and received in methadone dose in increments of 10 mg until symptoms resolved (mean in methadone dose required: 22%)

Efavirenz3 Case report 1 patient on methadone 100 mg a day for over one year; switched from nelfinavir/lamivudine/stavu-dine to an efavirenz containing regimen.

Four weeks after the introduction of efavirenz, patient reported tiredness, headache, cold sweats and shivering. Concentrations of (R)-methadone (active enantiomer of methadone) before and after the introduction of efavirenz were 168 and 90 ng/ml, respectively. Dose of methodone to 180 mg/day before symptoms disappeared.

Monitor for symptoms of opiate withdrawal (e.g. lacrimation, rhinorrhea, diaphoresis, restlessness, insomnia, dilated pupils, piloerection) and adjust methadone dose if nececssary.



Efavirenz4 Case report 3 HIV infected IV drug users on methadone treatment.

Opiate withdrawal symptoms emerged 4 to 7 days following the introduction of efavirenz. Methadone levels were obtained in one patient and were 65% lower with efavirenz than at baseline. Patients required a 66-133% in methadone dose to compensate.

Nevirapine, then Efavirenz5

Case report Patient stabilized on methadone 40 mg daily. Antiretroviral therapy changed from zidovudine/lamivudine to d4T/ddI/nevirapine, and later d4T/ddI/efavirenz.

2 days following change, patient experienced symptoms compatible with opiate withdrawal (i.e. cramps, tremor, rhinorrhea etc). Symptoms stopped with the discontinuation of nevirapine, and recurred with nevirapine rechallenge. Symptoms recurred again following change to efavirenz, in spite of dose to 80 mg/day. Methadone levels stable despite dose increase.

Nevirapine6 Case report 1 patient on methadone 80 mg/day for 3 years; switched from ddI/d4T/SQV-hgc/NFV after 1 month (because of ddI intolerance) to d4T/NFV/SQV-sgc/nevirapine.

One week following the change to a nevirapine containing regimen, the patient experience symptoms of methadone withdrawal (total body pain, nausea, vomiting, insomnia, sweats, sense of impending doom). Over the course of 4 weeks, the dose to 130 mg/day and her symptoms resolved.

Nevirapine7 Retrospective chart review.

7 patients on chronic methadone maintenance following initiation of treatment with nevirapine containing regimens.

Methadone withdrawal precipitated in all patients within 4-8 days of initiating treatment with nevirapine. Methadone levels were determined for 3 patients, and were subtherapeutic in each case. Dose necessary, and 4 patients chose to discontinue therapy.

Monitor for symptoms of opiate withdrawal (see under Efavirenz) and adjust methadone dose if nececssary.



Nevirapine8 Case series 5 patients on methadone maintenance program starting nevirapine based HAART.

4 of the 5 patients exhibited symptoms consistent with opiate withdrawal 6-15 days after beginning nevirapine therapy. Two patients discontinued therapy; two patients remained on therapy but required in methadone dose of 33% and 100%.

Nevirapine9 Prospective study 45 intravenous drug users, stabilized on methadone and treated with nevirapine, didanosine and lamivudine, all once a day.

30% of the 45 patients required in their methadone dose due to withdrawal symptoms.

Nevirapine10 Pharmacokinetic study 8 patients on stable daily methadone, beginning treatment with nevirapine based HAART.

Nevirapine methadone AUC by a mean of 50%. 6 of the 8 patients reported symptoms of methadone withdrawal from days 8-10 onwards of starting nevirapine, and received an in methadone dose in increments of 10 mg (mean in methadone dose required: 16%).

Nevirapine11 Pharmacokinetic study 24 patients on stable methadone, beginning treatment with nevirapine based HAART. 12-hour PK measurements done at baseline and after 28 days.

Nevirapine methadone AUC by mean of 40%; mean methadone dose by 24% (range 0-80%) during study.

PIs

Amprenavir (+ abacavir)12

Pharmacokinetic study Methadone blood concentrations were measured in five addict patients receiving methadone maintenance therapy before and after introduction of abacavir plus amprenavir for 14

Methadone concentrations by 35% (range 28-87%, p = 0.043). Two patients reported on several occasions nausea in the morning before the intake of the daily methadone dose, which is suggestive of a withdrawal reaction.


Antiretroviral Study Type Patient(s) Nature of interaction Recommendation days.

Amprenavir13, 14

Pharmacokinetic study 16 opiate dependent, HIV-patients on at least 30 days stable methadone treatment; methadone levels reassessed after 10 days of amprenavir 1200 mg bid.

Prospective, open-label study in HIV-negative subjects (n=19) maintained on methadone for at least 30 days, addition of amprenavir 1200 mg BID for 10 days resulted in delayed APV absorption, 13% AUC, 21% Cmin of active methadone enantiomer. The inactive S-enantiomer AUC and Cmin were decreased by 40% and 52%, respectively. No clinical evidence of methadone withdrawal was observed, and no methadone dosage was adjusted in any patient.

Compared to a non-matched historical control group, a 30%, 27%, and 25% in AUC, Cmax, and Cmin of amprenavir was observed. Clinical significance unclear.

Methadone dosage adjustment likely not necessary when coadministered with amprenavir. Monitor for amprenavir efficacy.

Indinavir15 Pharmacokinetic 12 HIV + patients on methadone 20 60 mg per day; indinavir 800 mg po q8h added.

No significant effect of indinavir on methadone AUC when compared to historical controls. No significant effect of methadone on indinavir AUC, but indinavir Cmin 50-100% and indinavir Cmax 16-36%, all vs. historical controls.

Combination appears safe.

Indinavir, Nelfinavir, Ritonavir, Saquinavir16

Case series Methadone levels measured prior to and at least one week following addition of a PI to stable dual RTI therapy in ten patients on methadone maintenance program.

Methadone concentrations unchanged in six patients switched to indinavir and one patient switched to saquinavir; methadone steady state concentrations 40-50% in one patient switched to ritonavir and two patients switched to nelfinavir.

Monitor for symptoms of opiate withdrawal (see under Efavirenz) with neflvinavir and ritonavir; adjust methadone dose if necessary.



Lopinavir/

ritonavir (Kaletra)17

Pharmacokinetic Eleven healthy volunteers received a single 5 mg dose of methadone. Methadone levels measured prior to and following ten days of lopinavir/ritonavir (400mg/100mg twice a day).

Lopinavir/ritonavir methadone AUC and Cmax 47%.

Lopinavir/ ritonavir vs. ritonavir18

Pharmacokinetic In two parallel, PK studies, healthy subjects on stable methadone received 7 days of either lopinavir/ritonavir 400/100 mg BID or ritonavir 100 mg BID.

Methadone AUC 26%, Cmax and Cmin 28% in presence of lopinavir/r, and was associated with a significant in number of opiate withdrawal symptoms. In contrast, methadone PK were not affected by ritonavir alone.

Lopinavir/ritonavir19

Pharmacokinetic study Eight HIV-infected patients on methadone maintenance (median dose, 80 mg; range, 40100 mg) initiated lopinavir/ritonavir plus 2 NRTIs.

A 36% in methadone AUC024h occurred after 14 days of lopinavir/ritonavir. However, none of the patients experienced opioid withdrawal symptoms or needed supplemental methadone added to their maintenance dose.

Observed decreases in methadone levels not always associated with opioid withdrawal symptoms; possible that lopinavir/ritonavir may produce stereoselective induction of methadone metabolism that would differentially decrease concentrations of the inactive S-isomer more than the active R-isomer.

Likely no need for routine methadone dose adjustment when initiating lopinavir/ritonavir; however, as a precaution it is still recommended to monitor for opioid withdrawal (see under Efavirenz) when



Lopinavir/ritonavir20

Observational study Twenty HIV-positive subjects maintained on methadone for >1 month initiated lopinavir/rtv HAART regimens. Changes in methadone dose and opioid withdrawal symptoms were assessed daily for 28 days. Median (range) methadone dose at study entry was 95 (40130) mg/d. Two subjects did not complete the observational period.

None of the 18 evaluable patients experienced symptoms of opioid withdrawal and no patients requested a change in methadone dosing during the evaluation period.

initiating therapy.

Nelfinavir21 Prospective pharmacokinetic study.

14 patients stabilized on a fixed methadone dose for at least 1 month before nelfinavir 1250 mg po bid for 8 days was added

Levels of (+)-methadone and (-)- methadone by 47% and 39%, respectively. No patient exhibited withdrawal symptoms, and no dosage adjustments were necessary.

Nelfinavir22 Retrospective case series

75 patients on stable methadone dose started on nelfinavir.

2 of 75 patients needed slight in methadone dose (10 mg/day). Otherwise, no impact of nelfinavir on methadone.

Nelfinavir23 Case report Patient on stable methadone dose of 100 mg daily, indinavir and ddC; d4T and nelfinavir added to regimen.

Within 6 weeks of medication change, patient began to complain of opiate withdrawal symptoms, which in severity over 3 months. Methadone dose at 1-2 week intervals, and subtherapeutic methadone levels documented until dose of 285 mg/d attained.

Observed decreases in methadone levels not always associated with opioid withdrawal symptoms. Monitor for symptoms of opiate withdrawal (see under Efavirenz) and adjust methadone dose if nececssary.



Nelfinavir24 Pharmacokinetic 16 non-HIV infected volunteers on stable methadone dose for 4 weeks and 13 controls; received NFV 1250 mg po bid for 5 days.

Nonsignificant in median NFV 12 hour trough with methadone. 12 hour AUC of M8 53% lower vs. control.

Nelfinavir25 Multi-site, retrospective

32 patients on stable methadone dose, receiving NFV based HAART; 84% of patients co-infected with hepatitis C.

17% of patients required methadone dose adjustments (mean 26 mg); otherwise, well tolerated combination.

Ritonavir/ Saquinavir26

Case report 1 patient on methadone 90 mg/day for 2 years. Antiretrovirals changed from indinavir/lamivudine/zido-vudine to ritonavir/saquinavir/stavudine because of virologic progression.

One week following initiation of ritonavir containing regimen, patient was admitted to hospital with shakiness, diaphoresis, blurred vision, anxiety and hypotension. Methadone plasma level on admission was 210 ng/ml (within therapeutic range, however no levels prior to initiation of ritonavir). Methadone dose was gradually to 130 mg/day.

Ritonavir/

Saquinavir27 Pharmacokinetic 12 HIV negative volunteers

on stable methadone dose evaluated before and after 14 days of once daily saquinavir/ritonavir (1600mg/100mg).

Clinically insignificant change in unbound methadone levels. 83% of subjects had Cmin of saquinavir > EC50.

Monitor for symptoms of opiate withdrawal (see under Efavirenz) and adjust methadone dose if nececssary.



Ritonavir/ Saquinavir28

24 hour pharmacokinetic study before and after 15 days of antiretroviral therapy to examine effect of ritonavir/saquinavir on methadone kinetics.

12 patients receiving stable methadone dose for at least 2 weeks.

S-methadone AUC 40%, and R-methadone AUC 32%. However, when change in methadone AUC expressed in terms of unbound methadone, change in AUC was no longer significant; no evidence of opiate withdrawal.

Ritonavir/

Saquinavir29

Retrospective 18 HIV + patients beginning once daily therapy with ritonavir 100 mg and saquinavir soft gel capsule 1600 mg and 5 HIV + patients beginning once daily therapy with ritonavir 200 mg and indinavir 1200 mg. All patients on methadone, 19 patients co-infected with hepatitis C.

No patient required methadone dose adjustment.

Reverse Transcriptase Inhibitors

Abacavir30 Pharmacokinetic study.

19 patients titrated to constant methadone dose (> 40 mg/day) over 14 days. Days 15-28, received concomitant methadone and abacavir.

Slight in clearance of methadone by abacavir; no statistically significant change in Cmax, half-life or renal clearance of methadone. Methadone causes slight delay in rate but not extent of abacavir absorption.

Combination appears safe.

Didanosine buffered tablets (ddI), stavudine (d4T)31

Pharmacokinetic study 17 patients on methadone maintenance and 10 control patients. Two pharmacokinetic studies were completed for each study subject and control

d4T AUC 23% ddI tablets AUC 57% Effect primarily related to reduced bioavailability.

No data to guide dose adjustments. Monitor for virologic failure.


Antiretroviral Study Type Patient(s) Nature of interaction Recommendation (one each for ddI and d4T).

Didanosine enteric-coated (EC) capsule32

Pharmacokinetic HIV-negative patients (n = 17) on stable methadone dose; randomized to EC or tablet formulation, and crossed-over to alternative regimen after PK monitoring over 24 hours; comparisons made to historical data in non-methadone patients.

ddI buffered tablet: trend to decreased ddI AUC in presence of methadone.

EC formulation provided ddI plasma AUC levels comparable to historical controls in non-methadone patients.

Combination of EC capsule of ddI and methadone appears safe, no dosage adjustments necessary.

Tenofovir33 Pharmacokinetic study 13 HIV-negative subjects on stable methadone received 14 days of tenofovir 300 mg daily; kinetics of methadone and its R- and S-isomers done at baseline and on day 14.

Short Opiate Withdrawal Scale (SOWS) questionnaire and pupillary diameter measurements also done at baseline and on day 14.

No change in kinetics of total methadone, R- and S-isomers when coadministered with tenofovir versus alone.

No clinical or laboratory signs of opiate-related toxicity or withdrawal (including changes in SOWS scores or pupillary diameters) were noted.

Methadone pharmacokinetics and dynamics not affected by tenofovir. Combination appears safe.

Zidovudine34 Pharmacokinetic study 14 HIV positive patients on methadone maintenance for at least 6 months and five control patients. Patients were receiving zidovudine 200 mg po every 4 hours.

Zidovudine AUC 43% vs. control. No effect on methadone maintenance.

Monitor for zidovudine related toxicities, such as nausea, vomiting, and bone marrow suppression.

Other opioid



Zidovudine36 Phamacokinetic within subject study.

8 patients started on acute methadone therapy as inpatients. Both oral and intravenous zidovudine pharmacokinetics determined before starting methadone, following acute methadone treatment and following two months of daily methadone.

Zidovudine AUC 41% during acute methadone treatment, and 29% during chronic treatment.

pharmacotherapies such as l-a-acetylmethadol LAAM, buprenorphine, or naltrexone not found to significantly affect zidovudine pharmacokinetics.35

Key: AUC = area under the concentration-time curve, bid = twice daily, Cmax = maximum plasma concentration, ddC = zalcitabine, ddI = didanosine, d4T = stavudine, EFV = efavirenz, HAART = highly active antiretroviral therapy, PI = protease inhibitor, NFV = nelfinavir, RTI = reverse transcriptase inhibitor, SQV-hgc = hard gel saquinavir

Please note: This chart summarizes some of the major drug interactions identified to date, based on current available data; other drug interactions may exist. Please use caution whenever adding/modifying therapy. The information in this table is intended for use by experienced physicians and pharmacists. It is not intended to replace sound professional judgment in individual situations, and should be used in conjunction with other reliable sources of information. Due to the rapidly changing nature of information about HIV treatment and therapies, users are advised to recheck the information contained herein with the original source before applying it to patient care.

References 1. Booker B, Smith P, Forrest A, Difrancesco R, Morese G, Cottone P, et al. Lack of effect of methadone (MET) on the pharmacokinetics

(PK) of delavirdine (DLV) & N-delavirdine [abstract A 490]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. December 16-19, 2001:14.

2. Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbons SE, Barry MG, et al. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. British Journal of Clinical Pharmacology 2001;51:213-7.

3. Marzolini C, Troillet N, Telenti A, Baumann P, Decosterd LA, Eap CB. Efavirenz decreases methadone blood concentrations. AIDS 2000;14:1291-2.

4. Boffito M, Rossati A, Dal Conte I, Reynolds H, Gibbons S, Back D, et al. Opiate withdrawal syndrome in new efavirenz recipients under methadone maintenance regimen (abstr). 1st IAS Conference on HIV Pathogenesis and Treatment, Buenos Aires. July 8-11, 2001.


5. Pinzani V, Faucherre V, Peyriere H. Methadone withdrawal symptoms with nevirapine and efavirenz. Annals of Pharmacotherapy 2000;34:405-7.

6. Heelon MW, Meade LB. Methadone withdrawal when starting an antiretroviral regimen including nevirapine. Pharmacotherapy 1999;19:471-2.

7. Altice FL, Friedland GH, Cooney E. Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. AIDS 1999;13:957-962.

8. Otero MJ, Fuertes A, Sanchez R, Luna G. Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert. AIDS 1999;13:1004-5.

9. Staszewski S, Haberl A, Gute P, Nisius G, Miller V, Carlebach A. Nevirapine/didanosine/lamivudine once daily in HIV-1 infected intravenous drug users. Antiviral Therapy 1998;3:55-6.

10. Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbons SE, Barry MG, et al. Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Clinical Infectious Diseases 2001;33:1595-7.

11. Stocker H, Kruse G, Kreckel P, Herzmann C, Arasteh K, Eskoetter H, et al. Nevirapine significantly reduces methadone levels in HIV-infected patients [abstract 867]. 2nd IAS Conference on HIV and Pathogenesis, Paris, France. July 14-17, 2003.

12. Bart PA, Rizzardi PG, Gallant S, Golay KP, Baumann P, Pantaleo G, et al. Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Ther Drug Monit 2001;23:553-5.

13. Hendrix CW, Wakeford J, Wire MB, Lou Y, Bigelow GE, Martinez E, et al. Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Pharmacother 2004;24:1110-21.

14. GlaxoSmithKline. Agenerase (amprenavir) Prescribing Information. Mississauga: June 28 2004 15. Cantilena L, McCrea J, Blazes D, Winchell G, Carides A, Royce C, et al. Lack of a pharmacokinetic interaction between indinavir and

methadone [abstract PI-74]. Clinical Pharmacology and Therapeutics 1999;65:135. 16. Beauverie P, Taburet AM, Dessalles MC, Furlan V, Touzeau D. Therapeutic drug monitoring of methadone in HIV-infected patients

receiving protease inhibitors. AIDS 1998;12:2510-1. 17. Bertz R, Hsu A, Lam W, Williams L, Renz C, Karol M, et al. Pharmacokinetic interaction between lopinavir/ritonavir (ABT-378/r) and other

non-HIV drugs [abstract P291]. 5th International Congress on Drug Therapy in HIV Infection, Glasgow, Scotland. October 22-26, 2000. 18. McCance-Katz EF, Rainey PM, Friedland G, Jatlow P. The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in

methadone-maintained patients. Clin Infec Dis 2003;37:476-82. 19. Clarke S, Mulcahy F, Bergin C, Reynolds HE, Boyle N, Barry M, et al. Absence of opioid withdrawal symptoms in patients receiving

methadone and the protease inhibitor lopinavir-ritonavir. Clin Infec Dis 2002;34:1143-5. 20. Stevens RC, Rapaport S, Maroldo-Connelly L, Patterson JB, Bertz R. Lack of methadone dose alterations or withdrawal symptoms during

therapy with lopinavir/ritonavir. J AIDS 2003;33:650-1. 21. Hsyu PH, Lillibridge JH, Maroldo L, Weiss WR, Kerr BM. Pharmacokinetic and pharmacodynamic interactions between nelfinavir and

methadone [abstract 87]. 7th Conference on Retroviruses and Opportunistic Infections, San Francisco. January 30-February 2, 2000. 22. Maroldo L, Manocchio S, Artenstein A, Weiss W. Lack of effect of nelfinavir mesylate on maintenance methadone dose requirement

(abstract WePeB4120). XIII International AIDS Conference, Durban, South Africa. July 9-14, 2000:60. 23. McCance-Katz EF, Farber S, Selwyn PA, O'Connor A. Decrease in methadone levels with nelfinavir mesylate [letter]. Am J Psychiatry

2000;157:481. 24. Smith PF, Booker BM, Difrancesco R, Morse GD, cottone PF, Murphy MK, et al. Effect of methadone or LAAM on the pharmacokinetics of

nelfinavir & M8 [abstract A-491]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. December 16-19, 2001:14.


25. Brown LS, Chu M, Aug C, Dabo S. The use of nelfinavir and two nucleosides concomitantly with methadone is effective and well-tolerated in HepC co-infected patients [abstract I-206]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. December 16-19, 2001:311.

26. Geletko SM, Erickson AD. Decreased methadone effect after ritonavir initiation. Pharmacotherapy 2000;20:93-94. 27. Shelton MJ, Cloen D, DiFrancesco R, Berenson C, Esch A, de Caprariis PJ, et al. The effects of once-daily saquinavir/minidose ritonavir

on the pharmacokinetics of methadone. J Clin Pharmacol 2004;44:293-304. 28. Gerber JG, Rosenkranz S, Segal Y, Aberg J, D'Amico R, Mildvan D, et al. The effect of ritonavir/saquinavir on the stereoselective

pharmacokinetics of methadone: results of AIDS clinical trials group (ACTG) 401. Journal of the Acquired Immune Deficiency Syndrome 2001;27:153-60.

29. Munsiff AV, Patel J. Regimens with once daily ritonavir + Fortovase are highly effective in PI-experienced HIV-HCV co-infected patients on methadone [abstract 684]. 39th Annual meeting of the Infectious Diseases Society of America., San Francisco, CA. October 25-28, 2001.

30. Sellers E, Lam R, McDowell J, Corrigan B, Hedayetullah N, Somer G, et al. The pharmacokinetics of abacavir and methadone following coadministration: CNAA1012 [abstract 663]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA. September 26-28, 1999:25.

31. Rainey PM, Friedland G, McCance-Katz EF, Andrews L, Mitchell SM, Charles C, et al. Interaction of methadone with didanosine and stavudine. Journal of the Acquired Immune Deficiency Syndrome 2000;24:241-8.

32. Friedland G, Rainey P, Jatlow P, Andrews L, Damle B, McCance-Katz E. Pharmacokinetics (pK) of didanosine (ddI) from encapsulated enteric coated bead formulation (EC) vs chewable tablet formulation in patients (pts) on chronic methadone therapy (abstract TuPeB4548). XIV International AIDS Conference, Barcelona. July 7-12, 2002:402-3.

33. Smith P, Kearney BP, Liaw S, Cloen D, Bullock JM, Haas CE, et al. Effect of tenofovir disoproxil fumarate on the pharmacokinetics and pharmacodynamics of total, R-, and S-methadone. Pharmacother 2004;24:970-7.

34. Schwartz EL, Brechbuhl AB, Kahl P, Miller MA, Selwyn PA, Friedland GH. Pharmacokinetic interactions of zidovudine and methadone in intravenous drug-using patients with HIV infection. Journal of the Acquired Immune Deficiency Syndrome 1992;5:619-26.

35. McCance-Katz EF, Rainey PM, Friedland G, Kosten TR, Jatlow P. Effect of opioid dependence pharmacotherapies on zidovudine disposition. Am J Addict 2001;10:296-307.

36. McCance-Katz EF, Rainey PM, P PJ, Friedland G. Methadone effects on zidovudine disposition (AIDS clinical trials group 262). Journal of the Acquired Immune Deficiency Syndrome 1998;18:435-43.

methadone interaction

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